A continuing long-range goal of the program is to examine in increasing depth the characteristics of renal function and some of the alterations that occur as renal mass is decreased in experimental animals and in patients with progressive chronic renal disease. Because of the increased functional requirements placed upon the surviving nephrons, certain of the control mechanisms governing the renal excretion of specific solutes become modified and specific component parts of this system exhibit exaggerated manifestations. Consequently, uremic patients and models with experimental renal disease offer the unique opportunity to examine these regulatory mechanisms in a manner which is often difficult to accomplish in the presence of a normal complement of nephrons. Over the next few years we hope to continue to exploit the unique biologic advantages of the model with a reduced nephron population in defining normal physiologic mechanisms. In addition, the contribution of adaptations in control systems to some of the abnormalities of the uremic state will be studied in detail. Recent studies on the biochemical adaptations occurring in the diseased kidney will be continued and extended. These studies relate to the metabolism of the kidney both in health and disease. Particular emphasis will be placed on the mechanisms which regulate gluconeogenesis and ammonia production. A second general area of interest and a major goal of the Program relates to the biology of ion transport. We have been particularly interested in the coupling between metabolism and cation transport and we have chosen to examine these interrelationships in isolated transport models. We will continue these studies on the coupling of metabolism and transport using both the isolated bladder of the toad and of the turtle.